Tazarotene-induced gene 1 interacts with Polo-like kinase 2 and inhibits cell proliferation in HCT116 colorectal cancer cells

Cell Biol Int. 2021 Nov;45(11):2347-2356. doi: 10.1002/cbin.11681. Epub 2021 Aug 5.

Abstract

Tazarotene-induced gene 1 (TIG1) is considered to be a tumor suppressor gene that is highly expressed in normal or well-differentiated colon tissues, while downregulation of TIG1 expression occurs in poorly differentiated colorectal cancer (CRC) tissues. However, it is still unclear how TIG1 regulates the tumorigenesis of CRC. Polo-like kinases (Plks) are believed to play an important role in regulating the cell cycle. The performance of PLK2 in CRC is negatively correlated with the differentiation status of CRC tissues. Here, we found that PLK2 can induce the growth of CRC cells and that TIG1 can prevent PLK2 from promoting the proliferation of CRC cells. We also found that the expression of PLK2 in CRC cells was associated with low levels of Fbxw7 protein and increased expression of cyclin E1. When TIG1 was coexpressed with PLK2, the changes in Fbxw7/cyclin E1 levels induced by PLK2 were reversed. In contrast, silencing TIG1 promoted the proliferation of CRC, and when PLK2 was also silenced, the proliferation of CRC cells induced by TIG1 silencing was significantly inhibited. The above research results suggest that TIG1 can regulate the tumorigenesis of CRC by regulating the activity of PLK2.

Keywords: Fbxw7; Polo-like kinases; cell proliferation; cyclin E1; tazarotene-induced gene 1.

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics
  • Cell Division / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Cyclin E / genetics
  • F-Box-WD Repeat-Containing Protein 7 / genetics
  • Gene Silencing / physiology
  • HCT116 Cells
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Oncogene Proteins / genetics
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics

Substances

  • CCNE1 protein, human
  • Cell Cycle Proteins
  • Cyclin E
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Membrane Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • RARRES1 protein, human
  • PLK2 protein, human
  • Protein Serine-Threonine Kinases